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By Dr.

Nabil Lymon Professor of Internal Medicine Mansoura University

Lecturers in Internal Medicine


I. Diabetic ketoacidosis Precipitating factors 1. Neglected treatment and inadequate administration of insulin. 2. Infections lead to increased insulin requirements. 3. Stressful conditions such as myocardial infarction, C.V. stroke, pregnancy, trauma, emotional stress which lead to increase in the counter-regulatory hormones of insulin leading to increase in the insulin requirements. 4. Endocrinal disorders: cushing, thyrotoxicosis, pheochromocytosis. 5. Drugs which decrease the insulin secretion such as:a. Steroids, Diuretics. b. Azathioprine, Diazoxide, Phenytoin.

Pathogenesis and clinical picture
A. Severe insulin deficiency leads to 1. Impaired glucose utilization as a source of energy leads to hyperglycemia, polyurea and dehydration which lead to muscle weakness, tachycardia and hypothermia. 2. The body begin to utilize fat as a source of energy leading to increased glycerol, free fatty acids with formation of ketone bodies (acetone, acetoacetic acid, B hydroxybuteric acid) which leads to:a. Acetone odour. b. Acidosis which lead to air hunger (Kausmaull respiration) c. Also ketonemia may lead to severe abdominal pain (acute abdomen)

Cont._________________________ __

3. Insulin deficiency leads to impaired K entery to the cells leading to hyper K which give the following manifestations:a. Atony of the skeletal muscles leads to muscle weakness and apathy. b. Atony of the GIT leads to ileus and gastric dilatation. c. Arrhythmia.

B. Confusion and rarely comma may develop due to the effect of 1. Ketone bodies. 2. Dehydration. 3. Electrolyte disturbance.

Differential diagnosis
Ketoacidosis Precipitating factors. Onset Skin Tongue Temperature Respiration Breath Blood pressure Effect of oral sugar See before Slow Dry and cold Dry Subnormal Kausmaull Acetone odour Low No effect Hopolycemia See later Rapid Wet Moist Normal Normal Normal Systolic pressure Rapid recover

1. Blood examination
a. Hyperglycemia more than 300 mg% and ketonemia. b. Acidosis (PH <7.3), increased FFA and triglycerides c. Electrolyte disturbances:- hyper K, hypo Na. d. Serum urea and creatinine increase due to hypovolemia.

2. Urine examination:- polyuria, glucosuria and ketonuria.

A. Prevention the patient is given guidelines to prevent this problem such as:
1.The daily dose of insulin is mandatory and its negligence is dangerous. 2.When the patient can't follow his usual diet due to severe illness e.g. pneumonia, he must eat or drink whatever he can tolerate. The patient must test for urine glucose and ketone bodies every 4 hours and if the tests show the need for extrainsulin, we can add 20% to the original dose (e.g. if the patient's usual dose is 40 U we can add 8 U).

B. Curative
1. Fluid replacement
a. Suitable regimen is as follow:- 1 litre in the In 1/2 h, followed by 1 litre in 1 h, another 1 litre in 1 h, 1 litre in 2 h, 1 litre in 3 h, and 1 litre in 4 h. b. 2 the total amount of the fluid deficit is given in 8 hours and the other 2 over the next 16 h. c. Normal saline is used at the start and changed to dextrose saline when blood glucose reaches 180 mg%.

2. Insulin regimen we can use one of these two methods:a. I V. insulin infusion by the use of infusion pump:- soluble insulin is diluted in 0.9 saline and 0.1 U/kg/h (6U/h) is given by the infusion. The infusion is continued until the patient is well enough (S.C.insulin is given before eating) and the insulin infusion is discontinued after meal. b. IM. route (soluble insulin) :- 20 U at the start, then 6 U/h till blood glucose reaches 200 mg%.

Cont._________________________ __
3. Electrolyte correction therapy as follow:- 20 mmol is added to every litre saline if K level is 3-4 meq/L. - 40 mmol is added to every litre saline if K level is less than 3 meq/L. - It is contraindicated to add K if there is oliguria or K level > 5 meq/L.

a. Kcl which is given from the second hour after insulin

b. Na HCO3:- 65 mmol over 30-60 min and can be repeated every hour when the PH <7.1 4. Treatment of the precipitating factors e.g infection. 5. Treatment of the complications:- see later.

1. Acute fatty infiltration of the liver. 2. Infection
a. Rhinocerebral infection with mucormycosis may complicate this condition b. Treatment with amphotricin B + necrotic tissue removal, improve the survival to about 60%.

3. Shock due to severe dehydration. 4. Vascular thrombosis due to dehydration and increased viscosity of the blood. 5. Pulmonary edema which may occur by the volume overload due to excess fluid. 6. Cerebral edema "rare but fatal"

Cause: It occurs 4-16 h. after initiation of therapy due to rapid decrease of blood glucose level which lead to movement of water into the intracellular space leading to brain edema.







ophthalmoplegia, confusion, coma.

Prevention: Avoid the rapid decrease of blood glucose and distribute the fluid replacement over 24 hours.

Treatment: Brain dehydrating measures e.g mannitol 12 gm/kg over 20 min.

II. Hyperglycemic hyperosmolar non ketotic coma (HONK)
A. It occurs in middle aged and elderly patients due to the presence of low level of insulin which is sufficient for prevention of lipolysis and ketosis and not enough to prevent hyperglycemia. B. The predisposing factors: see diabetic ketoacidosis.

Clinical picture
1. Severe hyperglycemia and dehydration which may lead to renal impairment. 2. Neurologic manifestations such as convulsions, stupors and coma. 3. Thrombotic complications may occur due to increased viscosity of the blood.

1. The same as in diabetic ketoacidosis but we give z tonic saline to decrease the serum osmolality which exceed 340 mosm/L (N.290 mosm/L). 2. Lower rate of insulin infusion 3U/h. 3. Lower rate of S.C. heparin to prevent thrombosis.

III. Lactic acidosis
1. Occur with: biguanide therapy especially phenformin. 2. The patient presents with acidosis (Kausmaull respiration), late CNS and CVS inhibition. 3. Plasma ketostix value: < ++ exclude diabetic ketoacidosis as a cause of metabolic acidosis. 4. Treatment:- by large amounts of bicarbonates.

IV. Hypoglycemia
1. Missed meal or Severe exercise after insulin or oral hypoglycemic agents. 2. Brittle diabetes mellitus. 3. Decreased elimination of insulin as in cases of renal failure. Clinical picture: 1. Adrenergic manifestations Begin when blood glucose < 50 mg% and leads to weakness, sweating, tremor, palpitation, irritability , tingling of the mouth and fingers ,hunger.

Cont._________________________ __ 2. Brain manifestations
Begin when blood glucose < 30 mg% and leads to headache hypothermia, visual disturbances, mental dullness, confusion, coma and dent 3. Masked symptoms of hypoglycemia may occur in the following conditions:a. Old age. b. During night. c. In alcoholics. d. During therapy with the following drugs:- βblockers tranqulizers. 4. Prolonged hypoglycemia leads to irreversible brain damage.

Low plasma glucose level < 50 mg% in male and < 45 mg% in female.

Differential diagnosis
1. From diabetic ketoacidosis:- see before. 2. From other causes of hypoglycemia:- see later.

1. Adrenergic reactions:- can be treated with oral CHO. 2. If there is coma or confusion:- I.V. glucose 25-50 gm 50% followed by constant infusion of glucose till the patient is able to eat. 3. Hypoglycemia due to sulphonylurea:- may persist for a long time (days) so glucose has to be infused for a long time.


Diabetic neuropathy
1. Mononeuropathy due to ischemia of the vaso nervosa. 2. Polyneuropathy

Accumulation of sorbitol: Normally 1% of glucose is converted to sorbitol by the effect of aldose reductase enzyme. In diabetics due to increased glucose level, sorbitol is converted to fructose by the effect of sorbitol dehydrogenase. The accumulated fructose leads to increased osmolarity of the cells leading to increased water and electrolyte content of the cells and damage of the axons, myelin schwan cells. Depletion of myoinositol: Its concentration in the peripheral nerves is 100 times than that of the plasma level. This concentration gradient is established by active transport (Na/K ATPase activity) which is defective in diabetics and this leads to disturbance of this concentration gradient.

Clinical picture
I. Mononeuropathy: Femoral, Ulnar, Median nerves, Cranial nerves 3,4,6. II. Trunkal neuropathy: pain in the distribution of one or more spinal nerves usually in the chest wall and the abdomen which may lead to acute chest pain or acute abdominal pain. III. Polyneuropathy
A. Sensory
1. Sensory affection is more than motor affection. 2. Early there is numbness and tingling sensation more by night and nocturnal calf spasm is common. 3. Late there is glove and stock hyposthesia

B. Motor

1. Diabetic amyotrophy "rare type":- bilateral asymmetrical weakness and wasting of the pelvic girdle and thigh muscles, recovery occur. 2. Diabetic neuropathic cachexia "more in elder males":- Bilateral symmetrical peripheral neuropathy, anorexia, severe depression and weight loss which give the impression of malignancy.

IV. Autonomic neuropathy
1. Genitourinary system
a. Bladder dysfunction

Early:- straining, dribbling, reduction in the stream force. Late:- bladder is distended with overflow incontinence.

b. Loss of testicular sensation which is used to differentiate organic from hysterical impotence. c. Impotence
- Parasympathetic affection leads to failure of erection. - Sympathetic affection leads to failure of ejaculation.

Cont._________________________ __
2. Cardiovascular dysfunction
a. Persistent tachycardia. b. Postural hypotension. c. Painless myocardial infarction.

3. 6ostrointestinal tract
a. 6astroparesis leads to slow emptying, distension and vomiting. b. Intermittent bouts of diarrhea which is severe, watery, nocturnal and alternating with constipation. c. Defects in the autonomic innervation of the internal anal sphincter leads to faecal incontinence.

Cont._________________________ __Sweating disturbance "due to affection of the 4.
sudomotor nerve fibres"
a. Gustatory sweating. b. Night sweating. c. Anhydrosis of the feet and legs with excessive sweating elsewhere. 5. Pupi/lacy changes: Argyll robertson pupil (miotic, irregular and eccentric).

6. Vasomotor disturbances:
a. Edema of the feet and leg due to loss of the vasomotor tone. b. IVleuropathic foot:- foot trauma leads to ulceration in the sole which may become infected leading to bone destruction and osteomyelitis.

1. Non steroidal anti-inflammatory drugs. 2. Phenytoin or Carbamazepine. 3. Tricyclic antidepressant. 4. Topically applied capsiacin "derived from red pepper". 5. Aldose reductase inhibitors.

Cardiovascular disorders
A. Microangiopathy: retinal renal vasa nervosa. B. Macroanqiopathy due to astherosclerosis
1. Cerebral:- thrombosis and ischemia. 2. Coronary astherosclerosis which differ from non diabetic in the following:a. Atypical anginal symptoms are more. b. Diffuse distal lesion + proximal lesion. c. Silent myocardial infarction. d. Complications of myocardial infarction are more. 3. Peripheral vessels:- intermittent claudications. 4. Renal:- renovascular hypertension due to renal artery asthersclerosis.

C. Cardiomyopathy:- due to myocardial hypertrophy and fibrosis due to deposition of mucopolysaccharide in the wall of the arterioles and capillary B.M. D. Blood pressure:- hypertension, postural hypotension.

1. Simple retinopathy. 2. Proliferative retinopathy. 3. Other diabetic complications affecting vision a. Changes in refraction "temporary changes"
- Hyperglycemia leads to myopia. - Hypoglycemia leads to hypermetropia.

b. Glaucoma is more frequent in diabetics. c. Senile cataract "occur at an earlier age".

I. Glomerular injury (Diabetic glomerulosclerosis) Pathogenesis It occurs in long standing DM (type I and type II) especially poorly controlled diabetes after about 10-20 years.There are two main types:A. Nodular glomerulosclerosis "Kimmelsteil-Wilson syndrome"
1. It is the classic lesion, constitute about 25% of cases. 2. There is deposition of glycoprotein in between and inside the glomerular capillaries. 3. Microaneurysms of small blood vessels with hyalinization of the afferent arterioles.

B. Diffuse glomerulosclerosis
1. The commonest form, constitute about 75% of the cases. 2. Diffuse thickening of the basement membrane. 3. Hyalinization of the afferent and efferent arterioles .

Stages A. Incipient nephropathy (good metabolic control can regress the lesion)
- Stage I:- hypertrophy and hyperf i Iteration leads to increased GFR >40%. - Stage II:- hyper fiIteration + microalbuminuria on exercise. - Stage III:- hyper fiIteration + constant microalbuminuria (excretion of > 50 mg/24 h). This stage may remain silent for up to 10-15 years.

B. Overt nephropathy
- Stage IV:- Proteinuria >500 mg/24 h (rarely the proteinuria exceed 5 gm/24 h). The GFR is decreased and hypertension is common. - Stage V:- End stage CRF. This azotemic period need long time to develop in diabetics, about 15 years from the onset of diabetes.

1. Diabetic control can reverse the microalbuminuria. 2. Hypertension has to be treated aggressively to delay the progression of the disease by ACE inhibitors which decrease albuminuria even in normotensive patients. 3. Low protein diet delay the progression. 4. Treatment of end stage CRF
a. Conservative measures in old age. b. Continuous ambulatory peritoneal dialysis. c. Transplantation is the treatment of choice in young patients.

II. Interstitial injury Acute pyelonephritis, acute necrotizing papillitis.

Other complications
I. Limited joint mobility
1. It is present in 15-30% of IDDM and NIDDM. 2. It may be a marker for increased risk for developing late diabetic complications in IDDM. 3. Tight waxy skin and limited full extension of the 5th finger followed by the other fingers can be found

II. Skin complications
1. Diabetic dermopathy:- Brown areas with depressed scar on healing. 2. Necrobiosis hipodica diabeticorum:- Plaque with raised erythematous border and depressed brownish c 3. Bullosis diabeticorum:-Tense blister which may ulcerate. 4. Acanthosis nigricans:- Skin with velvety appearance. 5. Eruptive exanthomas:-Yellow to red papules that may occur in response to trauma (Koebner phenomenon). More in uncontrolled diabetics who have severe hypertrig lyceridemia. 6. Lipodystrophy:-At the sites of insulin injection. 7. Scleroderma:- Hardening of the skin over the face, neck, upper limb.

III. Infections
- Skin infection: candida, staph., fungus e.g mucormycosis. - Chest infections: especially tuberculosis which follow diabetics like their shadows. - Renal infections: pyelonephritis, papillary necrosis. - Genital infections in females leading to severe pruritis vulvae.




Treatment of diabetes mellitus I. control A. Amount of calories calculated "caloric adjustment aim to control the body wt"
- Heavy workers:- 35 K cal/kg IBW. - Moderate active persons:- 30 Kcal/kg IBW. - Mild active persons:- 25 K cal/kg IBW. - For boys 1 year old:- 1000 Kcal/ day, add 100 Kcal for each year of age.

B. Proportion of food elements
- CHO:- 2-3gm/ kg. Supply the body by 50% of the calories. - Protein:- 1-29m/ kg. Supply the body by 20% of calories. - Fat:- 1gm/ kg. Supply the body by 30% of calories.

Cont._________________________ __Distribution of calories: The patient is given 3 C.
main meals and 3 snacks. D. Precautions as regard the diet
1. Avoid simple sugars and give fine fibers (non absorbable polysaccharides) as bran which delay the absorption of other CHO so the increase in blood glucose is gradual. 2. Type of protein which can be given:-fish, poultry and skimmed milk. 3. Give plenty of vegetables.

E. What is the value of weight reduction ?
1. Decrease Hepatic glucose production. 2. Decrease insulin resistance. 3. Increase B-cell function.

II. Oral therapy
A. Sulphonylurea group Mechanism of action
1. Stimulate insulin secretion (main action). 2. Decrease hepatic glucose production. 3. Increase sensitivity of insulin receptors. 4. Reverse the post binding defect of insulin action.

1. Old generation Acetohexamide Chloropropamide Tolzamide Tolbutamide 2. New generation Glibenclamide Glipizide Gliclazide Glimepiride (amaryl) 1.25-20 mg once or twice 2.5-40 mg once or twice 80-480 mg 1-8 mg up to 24 h up to 24 h up to 12 h up to 24 h Dose 250-1500 mg twice 100-500 mg once 500-3000 mg 2-3 times Duration 14 hours up to 60 hours 6-12 hours

100-1000 mg once or twice 14 hours

1. Acetohexamide, glibenclamide and glipizide are metabolised in the liver and kidney. 2. Chloropropamide and gliclazide are metabolised only in the kidneys. 3. Tolzamide and tolbutamide are metabolised only in the liver.

Side effects
1. Hypoglycemia which may be severe and prolonged especially with chloropropamide. 2. HypoNa due to increased ADH by chloropropamide. 3. Hepatitis and bone marrow depression (rare). 4. Skin reactions.

Drug interactions:- The hypoglycemic effect is:- Increased by:- NSAIb, sulphonamide, BB, H2 receptor antagonists. - Decreased by:- corticosteroids estrogen rifampicin diuretics, barbiturates.

B. Biguanide group

Mechanism of action
1. Decrease plasma glucose by reduction of gluconeogenesis. 2. Increase sensitivity of insulin receptors. 3. Decrease intestinal glucose absorption. 4. Decrease body weight through its anorexogenic effect.

Preparations and dosage
1. Phenformin: may induce lactic acidosis. 2. Metformin: 500-1000 mg tab are available. It should be used with caution in the elderly and contraindicated in patients with renal impairment.

Side effects
1. Mild self limited diarrhea, nausea, and anorexia. 2. Some patients complain of metallic taste in their mouth and abdominal discomfort. 3. Many of these side effects are transient and dose related and can be minimized by taking metformin with meals and titrating the dose and by decreasing the dosage.

C. Alpha glucosidose inhibitors "miglitol, acarbose" Mechanism They slow down the breakdown of disaccharides and polysaccharides and other complex CHO into monosaccharides on the brush border of the small intestine leading to delayed glucose absorption. Side effects
1. Flatulence, soft stools and mild abdominal discomfort. 2. They are dose related and transient, occuring during the 1st few weeks of therapy.

1. They don't cause hypoglycemia. 2. It is safer than sulfonylurea and biguanides in patients with kidney diseases and in the elder population. 3. It is also effective in patients with gestational diabetes manifested mainly by postprandial hyperglycemia. 4. It decrease the insulin requirements by 40% in patients with type I diabetes. 5. Decrease the daily fluctuation in blood glucose values.

Dose: 50-100 mg orally twice with meals. Acarbose must be titrated up very slowly in order to avoid side effects (start by 25 mg/day and increase by 25 mg/w).

D. Troglitazone "insulin sensitizer":- it acts by improving the insulin receptors. III. Insulin therapy Indications
1. All type I (IDDM) patients. 2. Patients with type II (NIDDM) in the following conditions:
a. Not responding to diet and oral hypoglycemic agents. b. During pregnancy and operations. c. During severe infection.

3. Patients with diabetic ketoacidosis

A. Type of insulin
Type 1. Short acting 2.Intermediate acting 3. Long acting Preparation Neutral (regular) Semilente Isophane (NPH) a. Lente b. Protamine zinc c. Ultralente 4. Biphasic Rapitard, mixtard Onset (hours) 1/2 1 3 2 6 4-6 1/2 Peak 3 3 8 8 12 12-16 8-12 Duration 6-8 6-8 16-24 24 24 30 16-24

B. Origin of insulin
1. Animal origin eg. bovine type. 2. Purified monocomponent which is non antigenic. 3. Human insulin prepared by genetic engineering by the recombinant DNA technology.

Insulin regimen 1. Conventional insulin therapy a. Two injections, 2/3 the dose before breakfast and 1/3 before lunch. b. 2/3 the dose intermediate insulin and 1/3 regular insulin. c. Begin by 20-30 U/day‘ and increase guided by the' response

2. Multiple subcutaneous insulin injection (MSII)
a. 25% of the dose is given as intermediate insulin before sleep. b. 75% of the dose is given as regular insulin before the three main meals.

3. Continous subcutaneous insulin infusion (CSII)
a. Small pump that deliver insulin SC. b. 40% of the total daily dose is given as the basal rate and the remainder as preprandial doses. c. It is indicated in the following conditions:-

- Pregnancy. - Renal transplantation. - Most patients with IDDM

Side effects
1. Insulin allergy which may be local or systemic reactions. 2. Hypoglycemia. 3. Insulin antibodies. 4. Insulin hpodystrophy: atrophy and displacement of S.C. fat at sites of insulin injections. 5. Insulin resistance due to: a. Obesity. b. Antibodies against insulin preparation. c. Antibodies against insulin receptors.

6. Somogi phenomenon: overdose of insulin given at night leads to hypoglycemia with night sweat and headache leading to increase in the counter regulatory hormones which may lead to hyperglycemia. This condition is treated by reduction of the evening insulin dose.

What do you know about dawn phenomenon? It refere to 'an early morning rise in plasma glucose requiring increase in the amount of insulin to maintain euglycemia. - Insulin analogues which may be: a. Short acting:- act within 5 minutes of its adminstration and last only for 2-3 hours. b. Long acting:- which resemble to great extent the basal insulin released in the body. - Oral insulin, nasal insulin, and rectal insulin are under trials. - Pancreatic transplantation. - Islet cell transplantation.


Gestational diabetes:- Impaired glucose tolerance (IGT) during pregnancy.
A:- I&T diagnosed before pregnancy and treated by diet alone. B:- Insulin treatment (duration <10 years) before pregnancy. C:- Insulin treatment (duration 10-20 years) before pregnancy. D:- Insulin treatment (duration >20 years) before pregnancy, Or the presence of chronic hypertension or simple retinopathy. F: - The presence of diabetic nephropathy. H:- The presence of coronary artery disease. R:- The presence of prof iferative retinopathy. T:- Prior renal transplantation.

The relation between diabetes and pregnancy

A. Effects of pregnancy on DM 1. Increase the need for insulin due to increased anti-insulin such as human placentallactogen and progesterone. 2. Decreased renal threshold for glucose. 3. Increased incidence of complications e.g nephropathy. B. Effects on the female 1. Abortion. 2. Premature labor. 3. Toxemia of pregnancy. 4. Postpartum hemorrhage. 5. Puerperal sepsis. C. Effects of DM on the baby 1. High birth weight. 2. Congenital anomaly especially anencephaly. 3. Hyaline membrane disease. 4. Hypoglycemia after birth hyperglycemia.

I. Pre-pregnancy planning Tight control should be initiated before pregnancy until the glycosylated Hb is normalized, this is because diabetes related congenital malformations occur by the 5th to 8th week. II. During pregnancy 1. Diet. small frequent meals to prevent nocturnal and preprandial hypoglycemia. 2. Insulin treatment and avoid oral hypoglycemic agents since they cause fetal beta cell hypertrophy and increase the tendency toward macrosomia and they have also teratogenic effects. 3. Monitor the diabetic control by: a. Home blood glucose monitoring:- keep FPG 60-110 and PPG <150 mg%. b. Glycosylated Hb every month. III. During labour:- maternal blood glucose is kept within 80-100mg% during labour by an infusion of dextrose 10 gm/h +regular insulin 1/2 -2 U/h. We must be cautious with insulin adminstration because there is increased insulin sensitivity during and after delivery.

Causes I. Fasting hypoglycemia 1. Increased Glucose utilization 1. With hyperinsulinemia: Insulin.  Exogenous insulin, sulphonylurea. 2. No hyperinsulinemia:a. Extrapancreatic tumors:- may be due to high level of insulin like growth factors from mesodermal tumors as fibroma sarcoma.  Systemic carnitine enzyme deficiency (an enzyme which is essential for carrying FFA to the mitochondria to be oxidized) so that all tissues become obligate glucose consumers.

2. Hepatic disorders a. Severe liver diseases: cirrhosis, fulminant hepatic failure. b. Enzyme defects: glycogen storage disease. 3. Hormonal deficiency:- hypopituitarism , Addison disease,hypothyroidism. 4. Substrate deficiency:- severe malnutrition, late pregnancy. 5. Drugs which lead to decreased glucose production: alcohol, BB, salicylates.

II. Postprandial hypoglycemia 1. Alimentary hypoglycemia: gastrectomy, gastrojejunostomy lead to rapid gastric emptying, brisk glucose absorption and excessive insulin release. 2. Early type II diabetes mellitus (I&T): the peak value of insulin occur after 2 hours or later when the absorption of CHO from the intestine has been completed. 3. Idiopathic type: which occur after large CHO meal. 4. Insulinoma.

III. Artifactual causes of hypoglycemia






leukemias when the leukocyte counts are markedly sample collection or storage or confusion between whole blood and plasma glucose values. The plasma glucose is about 15% higher than corresponding whole elevated. This reflect utilization of glucose by leukocytes after the blood sample has been drawn, such condition is not associated with symptoms.

Other artifactual hypog/ycemias may be seen with:Improper blood glucose values.

Clinical picture
Refere to diabetic hypoglycemia.

1. Fasting plasma glucose level less than 50 mg% in males and < 45 mg% in females.
a. If the amount of glucose required to correct the manifestations of hypoglycemia is less than 10 gm, the cause of fasting hypoglycemia is decreased production of glucose. b. If > 10 gm, the cause will be increased utilization of glucose.

2. The ratio of insulin (uU/ml) / plasma glucose (mg/dl) a. Normally less than 0.4 b. In patients with insulinoma, it is higher. 3. Determination of the plasma level of insulin, cortisol, thyroxine. 4. Liver and kidney function tests. 5. Abdominal ultrasonography or C.T for solid tumors

I. Fasting hypoglycemia A. The acute attack: see diabetic hypoglycemia. B. insulinoma 1. Surgical: resection of the tumor is the treatment of choice, if the tumor can't be localized stepwise pancreatectomy (from tail to head) is done. Resection is stopped once blood glucose rises. 2. Medical: in cases of preoperative preparation , and in non surgical cases. a. Diazoxide: 300-1200 mg/day ,IV or orally. b. Octreotide: 150-450 mg/day , 5C. c. Cytotoxic drugs: doxorubcin and streptozotocin for metastatic insulinoma.

II. Post-prandial (reactive hypoglycemia) 1. Diet (the main line of treatment) small frequent meals and avoid simple CHO. 2. Drugs a. Probanthine: 7.5 mg 2 h before meals. b. Phenytoin: 100-200 mg. It inhibits insulin secretion. c. Propranolon: 10 mg 2 h before meals. 3. Surgery inhibition of rapid entry of glucose into the intestine by putting a reversed jejunal segment near the gastric outlet. This is done Incases refractory to the previous measures.


Physiology 1. Vasopressin (A.D.H.) is secreted by the supraoptic muceli in the hypothalamus and migrate along the axons of these nuclei to the posterior pituitary. 2. Actions of A.D.H. a. Increased Absorption of H2 0 in the collecting tubules to maintain osmolality and volume of body fluids constant. b. Increased A.C. T.H. release from the anterior pituitary. c. It may enhance memory and learning. d. Constrict the arteriolar smooth ms. 3. Control of secretion a. Increased plasma osmolality: stimulate the osmoreceptor in the hypothalamus leading to increased A.D.H. secretion. b. Decreased blood volume: decrease inhibitory impulses .of the left atrium (which passes via the vagus) on A.D.H. release leads to increased A.D.H. secretion. c. Decreased blood pressure: stimulate the baroreceptors in the carotid sinus and aortic arch leading to increased A.D.H. secretion. d. Neural regulation: - Cholinergic and R- adrenergic stimuli :- stimulate A.D.H. - Atropine and a- adrenergic stimuli :- inhibit A.D.H.

I. Central D.I. 4 types of central DI are - Complete central DI : inability to secrete ADH. - Partial central Dl: ADH is secreted at a normal osmotic threshold but in subnormal amounts. - Defective osmoreceptor DI : AbH is not released in response to plasma osmolality but released in response to hypovolemia. - Reset osmoreceptor D.L : A.D.H. is released at a higher than normal osmotic threshold. A. Familial 1. Dominant or recessive inheritance. 2. DIDMOAD "wolfram syndrome" (DI., D.M., optic atrophy, nerve deafness).

B. Acquired
1. Trauma 2. Tumors: large pituitary tumors. 3. Infections: meningitis, encephalitis. 4. Infilteration: sarcoidosis 5. Infarction: sheehan syndrome. 6. Idiopathic: most common cause.

II. Nephroqenic D.I. A. familial: X- linked B. Acquired 1. Electrolyte disturbance: hypok or hyperca. 2. Chronic renal failure. 3. Drugs: demethylchlortetracycline, lithium. 4. Systemic: multiple myeloma, amyloidosis.

Clinical picture
1. Polyuria and polydepsia: urine volume > 2.5 L/day and may reach to 20 L/day. 2. Severe dehydration leads to weakness, psychic disturbance, prostration and death. 3. Rarely: insomnia, exhaustion, depression and constipation. May be weight loss in chronic cases with signs of dehydration. 4. Features of the underlying etiology.

I. Urine ex
1. Polyuria with low specific gravity (1001- 1004). 2. No pathological constituents. II. Localization of the site of the lesion 1. Dehydration test 1. Prevent the patient from drinking water for 4 - 18 h. 2. Follow up every hour for specific gravity and body weight. 3. We proceed to the next step if the patient lose 5% of his body weight during the test (to prevent hypotension) or i urine specific gravity becomes nearly stable in 3 successive samples. 4. Aquous A.D.H 5 U. is given S.C. and urine specific gravity is measured after one hour. 5. Interpretation: - Psychogenic polydepsia:- urine specific gravity increase at the end of the test and doesn't increase further after A.D.H. administration. - Central D.I.: urine specific gravity doesn't increase at the end of the test but increase after A.D.H. - Nephrogenic D.I.: no increase in the specific gravity at the end of the test or after A.D.H. adminstration.

2. Nicotine test 1. Normally 1-3 mg nicotine tartarate stimulates the hypothalamus to release A.D.H. leading to oliguria. 2. The response is -ve in hypothalamo-hypophyseal axis lesion. 3. Plain X- ray, C T, MRT on the sella turcica to exclude pituitary tumors. 4. Hypertonic Na cl 1. Normally 2.5 cc 2.5% solute/kg stimulate the osmoreceptors in the hypothalamus leading to oliguria. The response is -ve in osmoreceptor defects. 5. Blood ex. for urea, creatinine, K., Ca. 6. Plasma osmolality a. Increases in cases of diabetes insipidus. b. Decreases in cases of psychogenic polydepsia.

Differential diagnosis
From other causes of polyuria :see later

I. Central D.I. A. Hormone replacement 1. Aquous vasopressin 5 U/S.C./6h. 2. Vasopressin tannate in oil 5 U I.M./48h. 3. Desmopressin (minirine) 10-20 ug intra-nasal/ 12-24 h. B. Non hormonal agents (stimulate A.D.H)
1. Chloropropamide 500mg/ day. 2. Clafibrate 500mg / 4 times / day. 3. Carbamazepine 500mg / day.

II. Nephroqenic D.I. Hydrochlorothiazide or chlorothalidone 50 mg/ day. Na has to be restricted from the diet. So hypo Na occur leading to decreased amount of Na delivered to the loop of Henle and decreased water excretion.



I. Tumors release ADH 1. Oat cell carcinoma of the lung. 2. Cancer pancreas. 3. Hodgkin's lymphoma. 4. Thymoma. II. Non tumorous tissue release ADH or stimulate ADH release from the pituitary A. Chest disorders 1.Tuberculosis. 2. Lung abscess. 3. Pneumonia. 4. Empyema. 5. C.O.P.D. 6. +ve pressure respiration

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B. C. N. S. disorders
1. Skull fracture. 2. Subdural hematoma. 3. Subarachnoid Hge. 4. Acute encephalitis. 5. Tuberculous meningitis. 6. Purulent meningitis. 7. Drugs: chloropropamide, carbamazepine.

Symptoms Weight gain, weakness, lethargy, mental confusion, convulsions and coma. Laboratory findings a. Low BUN, creatinine, uric acid, albumin. b. Serum Na < 130 mmol/ L. c. Urine is almost always hypertonic in comparison to plasma and urinary Na > 20 mmol/ L.

1. Mild cases: fluid restriction to 0.8- 1L/ d. 2. Severe cases: 200- 300 ml 5% NaCl solution IN over several hours to increase Na level. 3. Demecloycline: interfere with renal action of ADH and may be useful when fluid restriction is impractical, but it has delayed onset of action.

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